The stem cell secretome refers to the full collection of bioactive molecules and factors secreted by stem cells into their environment. This includes soluble proteins (such as cytokines and growth factors), lipids, extracellular vesicles (like exosomes and microvesicles), and free nucleic acids. These secreted factors enable stem cells to communicate with other cells, supporting processes such as regulation of inflammation, tissue repair, immune modulation, and regeneration.
Pioneering discoveries into stem cell secretomes by one of Micregen’s founder’s in 1993 showed their capability of slowing and/or reversing certain disease states, meaning that a secretome-based treatment may be able to enhance regeneration.
This opened the door to a field of discoveries which use a cell-free approach.
Whilst the wider medical community continued to focus on transplanting whole mesenchymal stem cells, his research into stem cell secretomes progressed relatively undetected for several years.
Whole stem cell therapies are scientifically established as a means to promote tissue regeneration. However, such approaches are often limited by issues such as inefficient targeting of damaged tissues and challenges related to donor-recipient compatibility, as well as potential risks including graft rejection, graft versus host disease, and possible tumour development.
Secretome-based therapies seek to overcome many of these limitations by focusing on the cell’s soluble and vesicular products rather than transplanting the stem cells themselves. This approach aims to deliver regenerative effects while minimising immunological complications associated with introducing living cells into a recipient. (Camussi, Deregibus et al. 2013, Pinho, Cibrão et al. 2020).
Notably, the composition of the stem cell secretome is highly dynamic and responds to environmental cues such as disease, inflammation, or tissue injury. This adaptability allows the secretome to be tailored to the specific needs of the tissue microenvironment, enhancing repair and modulating immune responses accordingly.
Micregen’s research focuses on developing allogeneic mesenchymal stem cell-derived secretome products through our Secretomix® platform by guiding stem cells through proprietary processes and controlled environments that stimulate the secretion of optimally regenerative factors. These secretomes are then collected to create an off-the-shelf therapeutic candidate, free from whole stem cells. The goal is to provide a regenerative therapy that includes all of the benefits afforded to whole-cell transplantation whilst reducing or eliminating the complications that derive from introducing whole cells, offering a potentially safer and more targeted option for regenerative medicine.
The EV component of Micregen’s secretome products are able to access many areas of the body to facilitate repair and regeneration. Interestingly, our research has suggested that some EVs are able to cross the Blood Brain Barrier, providing the potential to treat certain neurological diseases, findings supported by others in the literature (Ramos-Zaldívar, Polakovicova et al. 2022).
Improved understanding of these mechanisms and optimising these effects in pre-clinical models is aimed to provide earlier and more effective clinical therapies using non-autologous stem cell-derived cell-free therapeutics for a variety of routes of administration.
The first human bone marrow transfusion was given to a patient with aplastic anaemia in 1939. By 1969 a clinical trial in Seattle successfully used allogeneic hematopoietic stem cell transplants from human leukocyte antigen (HLA) matched donors for the first time (Henig and Zuckerman 2014).
A decade later, this same technique was improved to achieve a cure rate of 50% in Acute Myeloid Leukemia patients in first remission (patients presenting with better clinical condition and with normal hematologic values) (Thomas, Buckner et al. 1979). This early research pointed to the power of the immune or body’s cellular system in these early cases to eradicate or improve disease.
In 1990, this work led to E. Donnall Thomas winning a Nobel Prize for his discoveries in cell transplantation for treating human disease.
In recent years, cell transplants from a matching donor have been effective in treatments beyond blood cancers. By the end of the first decade of the 21st century, whole stem cell transplants were being performed for many diseases.
Whole stem cell transplant regenerative therapies are well-established treatments; they are often found to be limited, with inefficient targeting to damaged tissue, donor-recipient compatibility, and come with a variety of known risks, including graft rejection, graft versus host disease and potential tumour development. Micregen’s research is focused on the development of mesenchymal stem cell-derived secretomes, which it is hoped will reduce many of these complications associated with whole cell transplantation.
Micregen Chief Scientist’s pioneering discoveries in 1993 on stem cell secretomes showed their capability of slowing and/or reversing certain disease states, meaning that a secretome-based treatment may be able to enhance regeneration. A secretome treatment may offer a simpler and potentially safer treatment than the stem cells themselves.
This opened the door to a field of discoveries which use a cell-free approach.
Whilst the wider medical community continued to focus on transplanting whole mesenchymal stem cells, his research into stem cell secretomes progressed relatively undetected for several years.
Micregen’s research and development team focused on identifying the repairing factors and optimising secretome production from stem cells. Allogeneic stem cell secretomes are being developed in our laboratories as regenerative cell-free products, which we call Secretomix®.
In so doing, the risks seen in whole-cell treatments have been reduced and, in some cases, eliminated (Camussi, Deregibus et al. 2013, Pinho, Cibrão et al. 2020).
Secretomix® is a multi-component biologic which acts to enhance multiple aspects of regeneration appropriate to many hallmarks of ageing. Micregen’s leading therapeutic candidate includes over 2,000 components – 450+ miRNA, Extracellular vesicles (EVs) including Exosomes, Cytokines, Anti-inflammatory Factors and Proteins, including Growth Factors.
The EV component of Micregen’s product is able to access many areas of the body to facilitate repair and regeneration. Interestingly, certain EVs have been shown to cross the Blood Brain Barrier, providing the potential to treat certain neurological diseases (Ramos-Zaldívar, Polakovicova et al. 2022).
Improved understanding of these mechanisms and optimising these effects in pre-clinical models allow earlier and more effective clinical therapies using non-autologous stem cell-derived cell-free therapeutics for a variety of routes of administration.
In addition, the clinical use of differentiated or undifferentiated stem cell secretomes provides an attractive, less invasive, safer alternative (minimising neoplasia, reducing immunological risks) to many whole mesenchymal stem cell treatments.